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Like a scene out of Hangover 3, the moment you remember that you don’t remember the night before…is gut-wrenching! It’s perfectly normal to feel riddled with guilt and shame as you wrack your brain for any evidence you may have made a fool of yourself the night before. Memory seemingly wiped clean, the best you can do to piece together the evening’s events is rummage through your pockets for clues, call up your partners in crime and prepare for the worst.

In the past it was thought that a blackout from being on the bevy was strictly an alcoholics problem. However, today research shows that while blackouts are indeed more common in alcoholics, for at least 50% of non-alcoholics that engage in rapid and excessive drinking, blacking out is a real risk.

It was also a premature idea that alcohol disrupts brain function and depression of the central nervous system in general, but now we know blackouts involve the failing of specific networks in the brain.

A comprehensive and critical review of the blackout science research published in Alcoholism: Clinical and Experimental Research, provides the most detailed view yet as to what happens to memories when your brain is blacking out (see diagram below).

Alcohol has been shown thus far to generally interfere with practically all stages of the memory process.

Short term-memory for example, can still be relatively intact when on a blackout. When short-term memory is fully functioning it tells us what is going on around us for the last 15-30 seconds or so, i.e. it tells us where we are and what we are doing essentially right now. It does this by tapping into our sensory memory (see brown labels in diagram below), the super-short term memory that gives us the ability to look/hear/taste/touch something, and remember what it felt like with just a second of observation.

Largely stored in the prefrontal cortex , you can think of short-term memory like RAM in a computer (see yellow labels in diagram below), it temporarily holds the info we are currently needing to get things done. As short-term memory still ‘kind-of’ functions during a blackout, detailed conversations are not impossible, although they may get annoyingly repetitive. And although definitely not recommended, managing complex tasks like driving are still just about feasible.

Yet in order to truly learn and retain information and remember the events of a night out on the town, it must be transferred from short-term memory into more permanent, long-term memory structures for storage as long-term memories (see orange labels in diagram below). It is the failing of this memory storage process — called memory encoding — that is completely kaput in a brain on a blackout.

Basically, when you blackout, memory encoding is where it all goes wrong.

Three brain structures in particular — the hippocampus, the frontal lobe and the medial septal — contribute to the blackout brain’s failed encoding of the night’s events.

The hippocampus, the horse-shoe shape colored green in the diagram, is found deep in the center of the brain. Its the head honcho when it comes to long-term memories, and in the case of blackouts, their non-existence.

In order to successfully create a memory for long-term storage specialized neurons in the hippocampus, called CA1 pyramidal cells, communicate with other essential areas of the brain. This way the hippocampus can receive information associated with sensory and short-term memory, as well as the emotional content of the memory being processed, and relay processed information back out.

Much like human’s when drunk, CA1 cells’ communication skills break down when under the influence. More specifically, it is thought that ethanol (and other drugs) activate a signal protein inside the cell called striatal-enriched protein tyrosine phosphatase, or STEP, which is found in high quantities in the hippocampus and striatum.

When activated by alcohol, STEP switches off proteins important for synaptic activity (the receiving and transmission of signals between neurons in the brain). STEP also results in the production of steroids that block synaptic strengthening and plasticity known as long-term potentiation (i.e. the strengthening of connections between neurons due to increases in activity that is the basis of learning and memory).

In summary, when on a blackout, alcohol gets STEP stepping all over the proper functioning of synapses, specifically disrupting the hippocampal CA1 cell communication needed for the process of recording a memory (encoding), and it also inhibits the neuroplastic strengthening of connections needed to make a long-term memory long-term.

The Medial Septal – The Gate Keeper

The medial septal is like the gatekeeper to information entering the hippocampus. It sends a type of brainwave called theta waves to the hippocampus. These theta waves change the excitement level of pyramidal cells in the hippocampus, thereby decreasing or increasing the likelihood of them being able to receive information from other structures in the brain.

When the pyramidal cells are excited new information has a greater chance of being processed than if the cells are suppressed. Alcohol disrupts the theta rhythm largely through suppressing the signal coming from the medial septal to the hippocampus.

The theory goes that without the theta wave excitatory signals coming from the medial septal, the gates to incoming information are closed, and the hippocampus can’t communicate effectively with other parts of the brain that are needed for long-term memory encoding. In fact, simply putting alcohol directly onto the medial septum causes memory loss.

Frontal Lobe – Details, Details, Details!

Key areas of the frontal lobe play important roles in both short–term memory and the formation and retrieval of long–term memories, including the prefrontal cortex well-known for its roles in rational decision making.

In long-term memory the prefrontal cortex has multiple roles, isolated to different regions within the brain structure. For example, the ventrolateral prefrontal cortex’s is specifically involved in the controlled selection of goal-relevant information. In other words, when recording a memory this part of the prefrontal cortex is involved in remembering the important parts of an event, like the specific gift you gave at a friend’s party, and not the less relevant info like the color of the pair of pants you were wearing at the time.

While the prefrontal cortex has shown to have reduced activity that is associated with memory impairments when under the influence, those that abuse alcohol have a very real risk of essentially drinking away the neurons in the frontal lobe, including the prefrontal cortex.

In fact, alcohol-induced dementia, a disease caused by alcohol abuse similar to dementia, is characterized by the “shrinkage” of the frontal lobe that is associated with both short-term and long-term memory loss.

However, as of yet, it is poorly understood how even acute alcohol use can leave the prefrontal cortex’s short-term memory functions relatively intact (remember? like RAM), but impair the encoding functions on route to the hippocampus. It may likely be due to the different effects alcohol has on the different types of neurons in the prefrontal cortex that are specifically important to either long-term or short-term memory.

The Big Picture

Understanding how alcohol can lead to memory loss is not only relevant to cases of alcohol and drug-addiction. The malfunctioning mechanisms, brain structures, neurons and molecules involved (like STEP) are the same as those involved in memory loss as a result of anxiety, stress and trauma, as well as in neurodegenerative diseases like Alzheimer’s and dementia. Understanding alcohol’s impact on memory may lead to the development of therapeutics and interventions that can restore these mechanisms in a variety of diseases and disorders, and give back the previous gift of long-term memories.